Proteinase inhibitors suppress the formation of granulation tissue in the carrageenin-induced inflammation in rats.

Abstract

Effect of proteinase inhibitors on the carrageenin-induced inflammation was studied. The formation of granulation tissue was markedly inhibited by a single injection of epsilon-amino-n-caproic acid n-hexyl ester (EACA hexyl ester, 300 mg/kg) into the carrageenin-airpouch immediately after carrageenin injection, whereas repeated injections of the inhibitor starting at 12 hr, 24 hr and 48 hr after carrageenin injection were less effective, slightly effective and ineffective, respectively. A dose-dependent inhibition of both the formation of granulation tissue and the migration of polymorphonuclear leukocytes (PMNs) into the inflammatory locus was found by a single injection of EACA hexyl ester into the carrageenin-airpouch immediately after carrageenin injection. Similarly, a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK, 50 mg/kg) and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK, 30 mg/kg) inhibited both the formation of granulation tissue and the migration of PMNs into the inflammatory locus. These results suggest that serine proteinase inhibitors such as EACA hexyl ester, TPCK and TLCK exert their anti-inflammatory actions by interfering with the initial inflammatory reactions including the migration of PMNs into inflammatory locus after carrageenin injection.